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Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase C epsilon

Chunhua Song1, Takaya Satoh, Hironori Edamatsu

  • 1Division of Molecular Biology, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

Oncogene
|November 22, 2002
PubMed

Insights

Platelet-derived growth factor activates phospholipase C epsilon (PLC-epsilon) via Ras and Rap1. Rap1, through its CDC25 homology domain, mediates prolonged PLC-epsilon activation, crucial for cell survival and proliferation.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Signal transduction

Background:

  • Phospholipase C epsilon (PLC-epsilon) is a key enzyme in cellular signaling.
  • It interacts with small GTPases Ras and Rap.
  • Understanding its regulation is crucial for cell function.

Purpose of the Study:

  • To investigate the molecular mechanisms of Ras and Rap1-mediated regulation of PLC-epsilon.
  • To elucidate the role of PLC-epsilon in cell survival and proliferation.
  • To explore the signaling cascade initiated by platelet-derived growth factor.

Main Methods:

  • Utilized a mutant platelet-derived growth factor receptor lacking phospholipase C gamma activation.
  • Employed ectopic expression of PLC-epsilon in BaF3 cells.
  • Investigated the role of the CDC25 homology domain in Rap1 activation.

Main Results:

  • Platelet-derived growth factor stimulation leads to persistent PLC-epsilon activation via Ras and Rap1.
  • Ras mediates the initial activation phase, while Rap1 drives prolonged activation.
  • The CDC25 homology domain is essential for Rap1-dependent sustained PLC-epsilon activation.
  • PLC-epsilon expression rescued BaF3 cells from apoptosis and promoted proliferation.

Conclusions:

  • Ras and Rap1 differentially regulate the temporal activation of PLC-epsilon.
  • Rap1-mediated signaling through its CDC25 homology domain is critical for sustained PLC-epsilon activity.
  • The phospholipase C signaling pathway is vital for hematopoietic cell survival and growth.

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